Abstract: The recent emergence of Zika in Latin America has caused over 1.5 million cases in 70 countries, with some 1,939 related cases of microcephaly since 2013. There is increasing evidence that Zika virus (ZIKV) and Dengue virus (DENV), both flaviviruses with high levels of cross-reactivity, have interdependent incidence trends, possibly due to host immunity and/or competition between the two viruses for mosquito infection. The effectiveness of any intervention approach will depend on the epidemiology of these co-circulating flaviviruses. We propose to examine the spatiotemporal epidemiological relationships of these viruses in a previously remote region in Esmeraldas province of northern coastal Ecuador, where the construction of a new road has created a gradient of urbanicity. This region exemplifies environmental, social, and demographic changes taking place worldwide. Our project team has 12 years of data on environmental change and infectious disease transmission in this region which we will build on to help address our study questions. Our overall objective is to understand the interplay between ZIKV and DENV transmission and how this interplay may change along the urbanicity spectrum. To do this we propose to characterize the epidemiology of both ZIKV and DENV simultaneously and to create a risk model that will inform interventions accounting for pathogen interaction and the level of urbanicity. DENV has one main vectorborne transmission pathway. ZIKV, in contrast, has multiple transmission pathways, e.g., mosquito and sexual transmission, and multiple mosquito species, therefore the relevant causal assemblages in more rural and more urban environments need to be carefully defined and their significance carefully assessed. Our overall question is this: what are the characteristics and mechanisms behind the co-circulation of ZIKV and DENV, and what key factors (e.g., human population density and diversity, social network structure, movement and migration patterns, infrastructure, vector populations, shifting economies) modify this interdependency? We propose a longitudinal study design at the village level that will allow us to estimate dengue and zika incidence over time.